Inhibitors of human immunodeficiency virus replication

Abstract

Compounds of Formulas I-VI, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth. Formula I is exemplified below:

What is claimed is: 
     
         1 . A compound of Formula I, including pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         A is a bond or is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, aryl, C 3 -C 6  cycloalkyl, C 2 -C 5  bicycloalkyl, —CO—, —CS—, —C(═N—CN)—, heterocyclyl, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene; 
         each R 1  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkylthioxy, benzyloxy, C 2 -C 4  alkynyl, aryl, carboxylic acid, cyano, halogen, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, thioxy, —CH 2 NH 2 , —(C 1 -C 4  alkyl)-heteroaryl, —CO—(C 1 -C 4  alkyl), —CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —NHCO—(C 1 -C 4  alkyl), —NHCO 2 —(C 1 -C 4  alkyl), —NHSO 2 —(C 1 -C 4  alkyl), —OCH 2 -aryl, —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, —N(R xa ) 2 , and nitro; 
         p is from 0 to 5; 
         R xa  and R xb  are independently selected from hydrogen, alkyl, or haloalkyl; 
         R y  is selected from C 2 -C 4  (dialkylamine) or nitrogen-containing heterocyclyl, and is attached to the parent fragment through its nitrogen; 
         X and X 1  are each are independently a bond or are selected from: 
       
       
         
           
           
               
               
           
         
         wherein the attachment of X and X 1  to the parent structure is such that the bond with the arrow is oriented toward the respective nitrogen shown in Formula I; provided, however, that when A is a bond, at least one X or X 1  is not a bond; 
         each n is independently from 0 to 2; 
         each R 4  is independently selected from hydrogen, C 1 -C 3  alkyl, C 1 -C 3  alkenyl, aryl, aryl(C 1 -C 2  alkyl), hydroxyl, and halogen, with the option for two R 4  on the same or adjacent carbon(s) to form a ring; 
         R 2a  and R 2b  are independently selected from hydrogen, C 1 -C 4  alkyl, C 3 -C 4  alkenyl, C 3 -C 5  alkynyl and C 3 -C 4  cycloalkyl, and each is optionally substituted with 1 to 3 substituents selected from halogen, hydroxyl, C 1 -C 2  alkoxy, and C 1 -C 2  haloaloxy; 
         G and G′ are each independently selected from; 
       
       
         
           
           
               
               
           
         
         each Y is independently oxygen or sulfur; 
         each J is a bond or is independently selected from aryl, heterocyclyl, or C 3 -C 7  cycloalkyl; 
         each R 5  is independently selected from hydrogen, C 1 -C 4  alkoxy, C 1 -C 4  alkyl, halogen, C 2 -C 5  bicycloalkyl, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 4  alkyl), —NHCON(C 1 -C 4  alkyl) 2 , —NHCO 2 (C 1 -C 4  alkyl), —OH, —SO 2 N(C 1 -C 4  alkyl) 2  and heterocyclyl; 
         each r is independently from 0 to 5; 
         each R 6  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, and C 3 -C 4  cycloalkyl, optionally substituted with halogen, hydroxyl, C 1 -C 2  alkoxy, or C 1 -C 2  haloalkoxy; 
         each L is independently selected from a five or six-member heteroaryl ring; 
         each R 7  is independently selected from C 1 -C 3  alkoxy, C 1 -C 3  alkyl, halogen, C 1 -C 3  haloalkoxy, C 1 -C 3  haloalkyl, —CONH 2 , —CN, —OH, —C 2 -C 5  alkynol, —NHCO(C 1 -C 3  alkyl), —NHCON(C 1 -C 3  alkyl) 2 , —NHCO 2 (C 1 -C 3  alkyl), —SO 2 N(C 1 -C 3  alkyl) 2 , and C 2 -C 6  alkyne optionally substituted with 1 to 2 halides; 
         each s is independently from 0 to 4; 
         E and E′ are each independently selected from C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 5 -C 8  bicycloalkyl, C 3 -C 7  cycloalkyl, aryl, heterocyclyl, and a C 1 -C 2  alkyl group containing any one of the following groups: C 5 -C 8  bicycloalkyl, C 3 -C 7  cycloalkyl, aryl, and heterocyclyl; 
         R 3a  and R 3b  are each independently selected from C 2 -C 4  alkenoxy, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, carboxyamide, halogen, —CN, —NHCO(C 1 -C 4  alkyl), —OH, C 1 -C 4  hydroxyalkyl, and —SO 2 N-heterocycle; and 
         q and q′ are each independently from 0 to 5; 
         wherein the attachment of each of “X”, “X 1 ” or N to “A” could be on the same or different atom(s) of “A”. 
       
     
     
         2 . The compound of  claim 1  wherein A is a bond. 
     
     
         3 . The compound of  claim 2  wherein at least one of X and X 1  are independently selected from: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1  wherein A is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, aryl, C 3 -C 6  cycloalkyl, C 2 -C 5  bicycloalkyl, —CO—, —CS—, —C(═N—CN)—, heterocyclyl, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene. 
     
     
         5 . The compound of  claim 4  wherein at least one of X and X 1  are a bond. 
     
     
         6 . A compound of Formula II, including pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
         wherein 
         A is a bond or is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, aryl, C 3 -C 6  cycloalkyl, C 2 -C 5  bicycloalkyl, —CO—, —CS—, —C(═N—CN)—, heterocyclyl, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene; 
         each R 1  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkylthioxy, benzyloxy, C 2 -C 4  alkynyl, aryl, carboxylic acid, cyano, halogen, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, thioxy, —CH 2 NH 2 , —(C 1 -C 4  alkyl)-heteroaryl, —CO—(C 1 -C 4  alkyl), —CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —NHCO—(C 1 -C 4  alkyl), —NHCO 2 —(C 1 -C 4  alkyl), —NHSO 2 —(C 1 -C 4  alkyl), —OCH 2 -aryl, —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, —N(R xa ) 2 , and nitro; 
         p is from 0 to 5; 
         R xa  and R xb  are independently selected from hydrogen, alkyl, or haloalkyl; 
         R y  is selected from C 1 -C 2  dialkylamine or nitrogen-containing heterocyclyl, and is attached to the parent fragment through its nitrogen; 
         X and X 1  are each are independently a bond or are selected from: 
       
       
         
           
           
               
               
           
         
         wherein the attachment of X, X 1  to the parent structure is such that the bond with the arrow is oriented toward the respective nitrogen shown in Formula II; provided, however, that when A is a bond, at least one X or X 1  is not a bond; 
         each n is independently from 0 to 2; 
         each R 4  is independently selected from hydrogen, C 1 -C 3  alkyl, C 2 -C 3  alkenyl, aryl, aryl(C 1 -C 2  alkyl), hydroxyl, halogen with the option for two R 4 s on same or adjacent carbon(s) to form a ring; 
         G and G′ are each independently selected from 
       
       
         
           
           
               
               
           
         
         each Y is independently oxygen or sulfur; 
         each J is independently a bond or selected from aryl, heterocyclyl, or C 3 -C 7  cycloalkyl; 
         each R 5  is independently selected from hydrogen, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), C 1 -C 4  alkyl, halogen, C 2 -C 5  bicycloalkyl, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 4  alkyl), —NHCON(C 1 -C 4  alkyl) 2 , —NHCO 2 (C 1 -C 4  alkyl), —OH, —SO 2 N(C 1 -C 4  alkyl) 2  and heterocyclyl; 
         each r is independently from 0 to 5; 
         each R 6  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, and C 3 -C 4  cycloalkyl, optionally substituted with halogen, hydroxyl, C 1 -C 2  alkoxy, or C 1 -C 2  haloalkoxy; 
         each L is independently selected from a five or six-member heteroaryl ring; 
         each R 7  is independently selected from C 1 -C 3  alkoxy, C 1 -C 3  alkyl, halogen, C 1 -C 3  haloalkoxy, C 1 -C 3  haloalkyl, —CONH 2 , —CN, —OH, —C 2 -C 5  alkynol, —NHCO(C 1 -C 3 alkyl), —NHCON(C 1 -C 3 alkyl) 2 , —NHCO 2 (C 1 -C 3  alkyl), and —SO 2 N(C 1 -C 3 alkyl) 2 , and C 2 -C 6  alkyne optionally substituted with 1 to 2 halides; 
         each s is independently from 0 to 4; 
         M and M′ are independently selected from C 1 -C 7  alkyl, C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 5 -C 8  bicycloalkyl, C 3 -C 7  cycloalkyl, aryl, and heterocyclyl; 
         each R 3a  and R 3b  is independently selected from C 2 -C 4  alkenoxy, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4 alkoxy)carbonyl, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, carboxyamide, halogen, —CN, —NHCO(C 1 -C 4  alkyl), —OH, C 1 -C 4  hydroxyalkyl, and —SO 2 N-heterocycle; and 
         q and q′ are each independently from 0 to 5; 
         wherein the attachment of “X”, “X 1 ” or N to “A” could be on the same or different atom(s) of “A”. 
       
     
     
         7 . A compound of Formula III, including pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
         wherein 
         A is a bond or is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, aryl, C 3 -C 6  cycloalkyl, C 2 -C 5  bicycloalkyl, —CO—, —CS—, —C(═N—CN)—, heterocyclyl, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene; 
         each R 1  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkylthioxy, benzyloxy, C 2 -C 4  alkynyl, aryl, carboxylic acid, cyano, halogen, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, thioxy, —CH 2 NH 2 , —(C 1 -C 4  alkyl)-heteroaryl, —CO—(C 1 -C 4  alkyl), —CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —NHCO—(C 1 -C 4  alkyl), —NHCO 2 —(C 1 -C 4  alkyl), —NHSO 2 —(C 1 -C 4  alkyl), —OCH 2 -aryl, —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, —N(R xa ) 2 , and nitro; 
         p is from 0 to 5; 
         R xa  and R xb  are independently selected from hydrogen, alkyl, or haloalkyl; 
         R y  is selected from C 1 -C 2  dialkylamine or a nitrogen-containing heterocyclyl, and is attached to the parent fragment through its nitrogen; 
         X and X 1  are each are independently a bond or are selected from: 
       
       
         
           
           
               
               
           
         
         wherein the attachment of X, X 1  to the parent structure is such that the bond with the arrow is oriented toward the respective nitrogen shown in Formula III; provided, however, that when A is a bond, at least one X or X 1  is not a bond; 
         each n is independently from 0 to 2; 
         each R 4  is independently selected from C 1 -C 3  alkyl, C 2 -C 3  alkenyl, aryl, aryl(C 1 -C 2  alkyl), hydroxyl, and halogen, with the option for two R 4  on the same or adjacent carbon(s) to form a ring; 
         J and J′ are independently a bond or are independently selected from aryl, heterocyclyl, or C 3 -C 7  cycloalkyl; 
         R 5a  and R 5b  are independently selected from hydrogen, C 1 -C 4  alkoxy, C 1 -C 4  alkyl, C 2 -C 4  (alkoxyalkyl), C 3 -C 4  cycloalkyl, halogen, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 4  alkyl), —NHCON(C 1 -C 4  alkyl) 2 , —NHCO 2 (C 1 -C 4  alkyl), —OH, —SO 2 N(C 1 -C 4  alkyl) 2  and heterocyclyl; 
         each r and r′ is independently from 0 to 4; 
         R 6a  and R 6b  are each independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, and C 3 -C 4  cycloalkyl, optionally substituted with halogen, hydroxyl, C 1 -C 2  alkoxy, or C 1 -C 2  haloalkoxy; 
         each R 3a  and R 3b  is independently selected from C 2 -C 4  alkenoxy, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, carboxyamide, halogen, —CN, —NHCO(C 1 -C 4  alkyl), —OH, C 1 -C 4  hydroxyalkyl, and —SO 2 N-heterocycle; and 
         q and q′ are independently from 0 to 4; 
         wherein the attachment of “X”, “X 1 ” or N to “A” could be on the same or different atom(s) of “A”. 
       
     
     
         8 . The compound as claimed in  claim 7 , wherein A is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, aryl with 1 to 2 rings, C 3 -C 6  cycloalkyl, —CO—, heterocyclyl with 1 to 2 rings, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene;
 each R 1  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 3  alkenyl, C 1 -C 2  alkoxy, aryl, carboxylic acid, cyano, halogen, C 1 -C 2  haloalkyl, C 1 -C 2  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, —CO—(C 1 -C 4  alkyl), CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, and —N(R xa ) 2 ; 
 p is from 0 to 4; 
 each R 4  is independently selected from hydrogen, C 1 -C 3  alkyl, aryl(C 1 -C 2  alkyl), hydroxyl, or halogen with the option for two “R 4 ”s on the same or adjacent carbon(s) to form a ring; and 
 n is from 0 to 2. 
 
     
     
         9 . The compound as claimed in  claim 8 , wherein A is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, aryl with 1 to 2 rings, C 3 -C 6  cycloalkyl, —CO—, heterocyclyl with 1 to 2 rings, nitrogen, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene;
 each R 1  is independently selected from the group of hydrogen, C 1 -C 4  alkyl, C 2 -C 3  alkenyl, C 1 -C 2  alkoxy, aryl, carboxylic acid, cyano, halogen, C 1 -C 2  haloalkyl, C 1 -C 2  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, —CO—(C 1 -C 4  alkyl), CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, and —N(R xa ) 2 ; 
 p is from 0 to 4; 
 each R 4  is independently selected from hydrogen, C 1 -C 3  alkyl, aryl(C 1 -C 2  alkyl), hydroxyl, or halogen with the option for two “R 4 ”s on the same or adjacent carbon(s) to form a ring; and 
 n is from 0 to 2. 
 
     
     
         10 . The compound as claimed in  claim 8 , wherein each R 3a  and R 3b  is independently selected from C 2 -C 4  alkenoxy, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, halogen, —CN, and —OH;
 q and q′ are independently from 0 to 3; 
 J and J′ are independently selected from 1-2 ring aryl, and 1-2 ring heteroaryl; 
 R 5a  and R 5b  are independently selected from hydrogen, C 1 -C 4  alkoxy, C 1 -C 4  alkyl, C 3 -C 4  cycloalkyl, halogen, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, C 3 -C 4  cycloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 2  alkyl), —NHCON(C 1 -C 2 alkyl) 2 , —NHCO 2 (C 1 -C 2  alkyl), —OH, and heterocyclyl; 
 r and r′ are independently from 0 to 4; and 
 R 6a  and R 6b  are independently selected from hydrogen, C 1 -C 4  alkyl, C 1 -C 4  alkenyl, or C 3 -C 4  cycloalkyl, and with the option for each to be substituted with halogen. 
 
     
     
         11 . The compound as claimed in  claim 10 , wherein each R 3a  and R 3b  is independently selected from C 2 -C 4  alkenyl, C 1 -C 2  alkoxy, C 1 -C 4  alkyl, C 1 -C 3  haloalkyl, C 1 -C 3  haloalkoxy, halogen, and —CN;
 q and q′ are independently from 0 to 3; 
 J and J′ are independently selected from 1-2 ring aryl, and 1-2 ring heteroaryl; 
 R 5a  and R 5b  are independently selected from the group of C 1 -C 4  alkoxy, C 1 -C 4  alkyl, C 3 -C 4  cycloalkyl, halogen, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, C 3 -C 4  cycloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 2  alkyl), —NHCON(C 1 -C 2 alkyl) 2 , —NHCO 2 (C 1 -C 2  alkyl), —OH, and heterocyclyl; 
 r and r′ are independently from 0 to 4; and 
 R 6a  and R 6b  are independently selected from hydrogen, C 1 -C 4  alkyl, C 1 -C 4  alkenyl, or C 3 -C 4  cycloalkyl, and with the option for each to be substituted with halogen. 
 
     
     
         12 . The compound as claimed in  claim 8 , wherein A is selected from CO, nitrogen, sulfur, oxygen, (CH 2 ) t  where t=1-4, —CH═CH—, —CH═C(Me)CH 2 —, —CH═CH—CH 2 —, —OCH 2 CH 2 O—, —NH(CO)NH—, cyclopentyl, cyclohexyl, phenyl, biphenyl, pyridine, pyrimidine, bipyrimidine, pyridazine, pyrazine, triazine, piperizine, pyrazole, thiophene, imidazole, isoxazole, indole, 1,3-dihydrobenzo[c][1,2,5]thiadiazole 2,2-dioxide, 1H-benzo[d]imidazol-2(3H)-one, imidazolidin-2-one, 2,3-dihydrophthalazine-1,4-dione, quinoxaline-2,3(1H,4H)-dione, 3-hydroxyquinoxalin-2(1H)-one, quinazoline-2,4(1H,3H)-dione, and ferrocene;
 each R 1  is independently selected from H, C 1 -C 4  alkyl, C 1 -C 2  haloalkyl, C 1 -C 2  alkoxy, C 1 -C 2  haloalkoxy, C 1 -C 4  hydroxyalkyl, OH, CO 2 H, cyano, halogen, C 1 -C 2  haloalkoxy, amine, and acetamide; 
 p is from 0 to 4; 
 R 4  is selected from hydrogen, C 1 -C 2  alkyl, or benzyl; and 
 n is from 0 to 2. 
 
     
     
         13 . The compound of  claim 12 , wherein each R 3a  and R 3b  is independently selected from halogen, C 1 -C 2  alkyl, C 1 -C 2  haloalkyl, C 1 -C 2  alkoxy, and C 1 -C 2  haloalkoxy;
 q and q′ are independently from 0 to 2;   J and J′ are each independently selected from phenyl, pyridine, pyrimidine, pyrazine, pyridazine, benzothiazole, benzothiazolone, benzothiadiazole, benzodioxole, benzoxazolone, benzisothiazole, 1-methylpyridin-2(1H)-one, 2,3-dihydrobenzo[b][1,4]dioxine, indazole, benzimidazole, and quinoxaline;   R 5a  and R 5b  are each selected from hydrogen, C 1 -C 4  alkyl, C 3 -C 4  cycloalkyl, C 1 -C 2  alkoxy, C 1 -C 2  haloalkoxy, C 1 -C 2  haloalkyl, methylcarbamate, benzyl, morpholinyl, halide, and CN;   r and r′ are independently selected from 0 to 2; and   R 6a  and R 6b  are independently selected from hydrogen, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, and C 1 -C 4  alkenyl.   
     
     
         14 . A compound of Formula IV, including pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
         wherein 
         A is a bond or is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, aryl, C 3 -C 6  cycloalkyl, —C 2 -C 5  bicycloalkyl, —CO—, —CS—, —C(═N—CN)—, heterocyclyl, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene; 
         each R 1  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkylthioxy, benzyloxy, C 2 -C 4  alkynyl, aryl, carboxylic acid, cyano, halogen, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, thioxy, —CH 2 NH 2 , —(C 1 -C 4  alkyl)-heteroaryl, —CO—(C 1 -C 4  alkyl), —CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —NHCO—(C 1 -C 4  alkyl), —NHCO 2 —(C 1 -C 4  alkyl), —NHSO 2 —(C 1 -C 4  alkyl), —OCH 2 -aryl, —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, —N(R xa ) 2 , and nitro; 
         p is from 0 to 5; 
         R xa  and R xb  are independently selected from hydrogen, alkyl, or haloalkyl; 
         R y  is selected from C 1 -C 2  dialkylamine or a nitrogen-containing heterocyclyl and is attached to the parent fragment through its nitrogen. 
         X and X 1  are each are independently a bond or are selected from: 
       
       
         
           
           
               
               
           
         
         wherein the attachment of X, X 1  to the parent structure is such that the bond with the arrow is oriented toward the respective nitrogen shown in Formula IV; provided, however, that when A is a bond, at least one X or X 1  is not a bond; 
         each n is independently from 0 to 2; 
         each R 4  is independently selected from C 1 -C 3  alkyl, C 2 -C 3  alkenyl, aryl, aryl(C 1 -C 2  alkyl)-, hydroxyl, and halogen, with the option for two R 4  on same or adjacent carbon(s) to form a ring; 
         J and J′ are independently a bond or selected from aryl, heterocyclyl, or C 3 -C 7  cycloalkyl; 
         each R 5a  and R 5b  is independently selected from hydrogen, C 1 -C 4  alkoxy, C 1 -C 4  alkyl, C 2 -C 4  (alkoxyalkyl), C 3 -C 4  cycloalkyl, halogen, C 1 -C 4  cycloalkyl, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 4  alkyl), —NHCON(C 1 -C 4  alkyl) 2 , —NHCO 2 (C 1 -C 4  alkyl), —OH, —SO 2 N(C 1 -C 4  alkyl) 2  and heterocyclyl; 
         r and r′ are independently from 0 to 4; 
         L and L′ are independently selected from a five or six-member heteroaryl ring; 
         each R 7a  and R 7b  is independently selected from C 1 -C 3  alkoxy, C 1 -C 3  alkyl, halogen, C 1 -C 3  haloalkoxy, C 1 -C 3  haloalkyl, —CONH 2 , —CN, —OH, C 2 -C 5  alkynol, —NHCO(C 1 -C 3  alkyl), —NHCON(C 1 -C 3  alkyl) 2 , —NHCO 2 (C 1 -C 3  alkyl), and —SO 2 N(C 1 -C 3  alkyl) 2 , and C 2 -C 6  alkyne optionally substituted with 1 to 2 halides; 
         s and s′ are independently from 0 to 4; 
         each R 3a  and R 3b  is independently selected from C 2 -C 4  alkenoxy, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4 alkoxy)carbonyl, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, carboxyamide, halogen, —CN, —NHCO(C 1 -C 4  alkyl), —OH, C 1 -C 4  hydroxyalkyl, and —SO 2 N-heterocycle; and 
         q and q′ are independently from 0 to 4; 
         wherein the attachment of “X”, “X 1 ” or N to “A” could be on the same or different atom(s) of “A”. 
       
     
     
         15 . The compound as claimed in  claim 13 , wherein J and J′ are each independently selected from phenyl, pyridine, pyrimidine, pyrazine, pyridazine, benzothiazole, benzothiazolone, benzothiadiazole, benzodioxole, benzoxazolone, benzisothiazole, 1-methylpyridin-2(1H)-one, 2,3-dihydrobenzo[b][1,4]dioxine, indazole, benzimidazole, and quinoxaline;
 R 5a  and R 5b  are each independently selected from hydrogen, C 1 -C 4  alkyl, C 3 -C 4  cycloalkyl, C 1 -C 2  alkoxy, C 1 -C 2  haloalkoxy, C 1 -C 2  haloalkyl, methylcarbamate, benzyl, morpholinyl, halide, and CN; 
 r and r′ are independently from 0 to 2; and 
 L and L′ are independently selected from a pyridine or an imidazole ring that is attached to the central parental structure through an adjacent carbon atom; and 
 each of R 7a  and R 7b  is independently selected from hydrogen, a C 2 -C 5  alkyne that is optionally substituted with 1 to 2 halide, or a C 2 -C 5  alkynol. 
 
     
     
         16 . A compound of Formula V, including pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
         wherein 
         A is a bond or is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, aryl, C 3 -C 6  cycloalkyl, —C 2 -C 5  bicycloalkyl, —CO—, —CS—, —C(═N—CN)—, heterocyclyl, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene; 
         each R 1  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkylthioxy, benzyloxy, C 2 -C 4  alkynyl, aryl, carboxylic acid, cyano, halogen, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, thioxy, —CH 2 NH 2 , —(C 1 -C 4  alkyl)-heteroaryl, —CO—(C 1 -C 4  alkyl), —CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —NHCO—(C 1 -C 4  alkyl), —NHCO 2 —(C 1 -C 4  alkyl), —NHSO 2 —(C 1 -C 4  alkyl), —OCH 2 -aryl, —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, —N(R xa ) 2 , and nitro; 
         p is from 0 to 5; 
         R xa  and R xb  are independently selected from hydrogen, alkyl, or haloalkyl; 
         R y  is selected from C 1 -C 2  dialkylamine or a nitrogen-containing heterocyclyl and is attached to the parent fragment through its nitrogen; 
         X and X 1  are each are independently a bond or are selected from: 
       
       
         
           
           
               
               
           
         
         wherein the attachment of X and X 1  to the parent structure is such that the bond with the arrow is oriented toward the respective nitrogen shown in Formula V; provided, however, that when A is a bond, at least one X or X 1  is not a bond; 
         each n is independently from 0 to 2; 
         each R 4  is independently selected from C 1 -C 3  alkyl, C 2 -C 3  alkenyl, aryl, aryl(C 1 -C 2  alkyl)-, hydroxyl, and halogen, with the option for two R 4  on same or adjacent carbon(s) to form a ring; 
         J and J′ are independently a bond or selected from aryl, heterocyclyl, or C 3 -C 7  cycloalkyl; 
         R 5a  and R 5b  are independently selected from hydrogen, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), C 1 -C 4  alkyl, halogen, C 3 -C 4  cycloalkyl, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 4  alkyl), —NHCON(C 1 -C 4 alkyl) 2 , —NHCO 2 (C 1 -C 4  alkyl), —OH, —SO 2 N(C 1 -C 4  alkyl) 2  and heterocyclyl; 
         r and r′ are independently from 0 to 4; 
         R 6b  is selected from hydrogen, C 1 -C 4  alkyl, C 1 -C 4  alkenyl, and C 3 -C 4  cycloalkyl, optionally substituted with halogen, hydroxyl, C 1 -C 2  alkoxy, or C 1 -C 2  haloalkoxy; 
         L is selected from a five or six-member heteroaryl ring; 
         R 7a  is selected from C 1 -C 3  alkoxy, C 1 -C 3  alkyl, halogen, C 1 -C 3  haloalkoxy, C 1 -C 3  haloalkyl, —CONH 2 , —CN, OH, C 2 -C 5  alkynol, —NHCO(C 1 -C 3  alkyl), —NHCON(C 1 -C 3  alkyl) 2 , —NHCO 2 (C 1 -C 3  alkyl), and —SO 2 N(C 1 -C 3  alkyl) 2 , and C 2 -C 6  alkyne optionally substituted with 1 to 2 halides; 
         each s is independently from 0 to 4; 
         each R 3a  and R 3b  is independently selected from C 2 -C 4  alkenoxy, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4 alkoxy)carbonyl, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, carboxyamide, halogen, —CN, —NHCO(C 1 -C 4  alkyl), —OH, C 1 -C 4  hydroxyalkyl, and —SO 2 N-heterocycle; and 
         q and q′ are independently from 0 to 4; 
         wherein the attachment of “X”, “X 1 ” or N to “A” could be on the same or different atom(s) of “A”. 
       
     
     
         17 . A compound of Formula VI, including pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
         wherein 
         A is a bond or is selected from C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, aryl, C 3 -C 6  cycloalkyl, —C 2 -C 5  bicycloalkyl, —CO—, —CS—, —C(═N—CN)—, heterocyclyl, nitrogen, sulfur, oxygen, —O—(C 2 -C 4  alkyl)-O—, —N(R xa )CON(R xb )—, and ferrocene; 
         each R 1  is independently selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4  alkoxy)carbonyl, C 1 -C 4  alkylthioxy, benzyloxy, C 2 -C 4  alkynyl, aryl, carboxylic acid, cyano, halogen, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, heterocyclyl, hydroxy, C 1 -C 4  hydroxyalkyl, thioxy, —CH 2 NH 2 , —(C 1 -C 4  alkyl)-heteroaryl, —CO—(C 1 -C 4  alkyl), —CO(R y ), —CON(R xa ) 2 , —NHCON(R xa ) 2 , —NHCO—(C 1 -C 4  alkyl), —NHCO 2 —(C 1 -C 4  alkyl), —NHSO 2 —(C 1 -C 4  alkyl), —OCH 2 -aryl, —SO 2 —(C 1 -C 4  alkyl), —SO 2 —N(R xa ) 2 , —SO 2 -heterocyclyl, —N(R xa ) 2 , and nitro; 
         p is from 0 to 5; 
         R xa  and R xb  are independently selected from hydrogen, alkyl, or haloalkyl; 
         R y  is selected from C 1 -C 2  dialkylamine or a nitrogen-containing heterocyclyl and is attached to the parent fragment through its nitrogen; 
         X and X 1  are each are independently a bond or are selected from: 
       
       
         
           
           
               
               
           
         
         wherein the attachment of X and X 1  to the parent structure is such that the bond with the arrow is oriented toward the respective nitrogen shown in Formula VI; provided, however, that when A is a bond, at least one X or X 1  is not a bond; 
         each n is independently from 0 to 2; 
         each R 4  is independently selected from C 1 -C 3  alkyl, C 1 -C 3  alkenyl, aryl, aryl(C 1 -C 2  alkyl)-, hydroxyl, and halogen, with the option for two R 4  on same or adjacent carbon(s) to form a ring; 
         J′ is a bond or is selected from aryl, heterocyclyl, or C 3 -C 7  cycloalkyl; 
         R 5b  is selected from hydrogen, C 1 -C 4  alkoxy, C 1 -C 4  alkyl, C 2 -C 4  (alkoxyalkyl), C 3 -C 4  cycloalkyl, halogen, C 1 -C 4  haloalkoxy, C 1 -C 4  haloalkyl, —CONH 2 , —CN, —NHCO(C 1 -C 4  alkyl), —NHCON(C 1 -C 4  alkyl) 2 , —NHCO 2 (C 1 -C 4  alkyl), —OH, —SO 2 N(C 1 -C 4  alkyl) 2  and heterocyclyl; 
         r′ is from 0 to 4; 
         R 6b  is selected from hydrogen, C 1 -C 4  alkyl, C 2 -C 4  alkenyl, and C 3 -C 4  cycloalkyl, optionally substituted with halogen, hydroxyl, C 1 -C 2  alkoxy, or C 1 -C 2  haloalkoxy; 
         Q is a bond or is selected from heterocycle and a —CON(C 1 -C 3  alkyl) 2  with the option for the two alkyl groups together with the nitrogen atom to which they are attached to form a heterocycle; 
         R 8  is selected from hydrogen, C 1 -C 2  alkyl and C 1 -C 2  alkyl-S—; 
         each R 3a  and R 3b  is independently selected from C 2 -C 4  alkenoxy, C 2 -C 4  alkenyl, C 1 -C 4  alkoxy, C 2 -C 4  (alkoxyalkyl), (C 1 -C 4 alkoxy)carbonyl, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, carboxyamide, halogen, —CN, —NHCO(C 1 -C 4  alkyl), —OH, C 1 -C 4  hydroxyalkyl, and —SO 2 N-heterocycle; and 
         q and q′ are independently from 0 to 2; 
         wherein the attachment of “X”, “X 1 ” or N to “A” could be on the same or different atom(s) of “A”. 
       
     
     
         18 . A composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier, excipient, and/or diluent. 
     
     
         19 . A method of treating method of treating HIV infection comprising administering a therapeutically effective amount of a compound of  claim 1  to a patient.